Related Experiment Videos
Antiapoptotic bcl-2 and bcl-xL in advanced malignant melanoma
U Leiter1, R M Schmid, P Kaskel
1Department of Dermatology, University of Ulm, Germany.
Abstract:
Apoptosis is an important cofactor in the pathogenesis of a plethora of malignancies. However, little is known about modulation of the expression of bcl gene family in melanocytic tumors. To determine the role of bcl-2, bcl-x and bax in melanocytic tumors we investigated the differential expression of these genes via RT-PCR in tissue samples from human benign nevi, primary melanomas and melanoma metastases in comparison with normal skin. Bcl-2 was strongly expressed in 14/16 metastases (87.5%), whereas only 7/13 primary melanomas (53%), 7/15 nevi (46%) and 7/16 normal tissue samples (43%) showed expression of bcl-2 (P < 0.05). There was a strong indication of a correlation between tumor thickness and bcl-2 expression in nodular malignant melanomas. Expression of bcl-x was found in 16/16 melanoma metastases (100%), 11/13 primary melanomas (84%), 12/15 nevi (80%) and 10/16 normal tissue samples (62%) (P < 0.05). Bcl-xL expression increased from primary melanoma to melanoma metastases, whereas bcl-xS showed a decreasing expression level during melanoma progression. No differences in bax expression were seen between melanoma metastases, primary melanoma, nevi and normal tissue. Immunohistochemical investigations of another 53 tissue samples showed similar results. Our results strongly indicate that bcl-2 and bcl-xL gene expression increases with progression of malignant melanoma. Bcl-2 and bcl-xL expression could reflect an increased malignant potential caused by an inhibition of apoptosis and growth advantage for metastatic melanoma cells.
Insights
Melanoma progression is linked to increased expression of bcl-2 and bcl-xL genes, which may inhibit apoptosis and promote tumor growth. This suggests these genes play a role in the malignancy of melanoma.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Apoptosis is crucial in cancer development.
- The role of the bcl gene family in melanocytic tumors is not well understood.
Purpose of the Study:
- To investigate the differential expression of bcl-2, bcl-x, and bax genes in melanocytic tumors.
- To determine the association of these genes with melanoma progression.
Main Methods:
- RT-PCR was used to analyze gene expression in benign nevi, primary melanomas, melanoma metastases, and normal skin.
- Immunohistochemistry was performed on additional samples.
Main Results:
- Bcl-2 expression was significantly higher in melanoma metastases (87.5%) compared to primary melanomas (53%), nevi (46%), and normal skin (43%).
- Bcl-xL expression increased from primary melanoma to metastases, while bcl-xS expression decreased during progression.
- No significant differences in bax expression were observed across the different tissue types.
Conclusions:
- Increased bcl-2 and bcl-xL gene expression correlates with melanoma progression.
- These gene expression changes may indicate an increased malignant potential by inhibiting apoptosis and conferring a growth advantage to metastatic melanoma cells.